Magnetic Particle Actuation

ABSTRACT

Magnetic particle actuating systems may include a magnet system configured to generate a magnetic field that includes a field-free region. A corresponding control system can be configured to control the magnet system to create a field-free region at least partially matching a target region. An excitation system can be configured to generate an excitation field to cause actuation of magnetic nanoparticles in an actuation region.

CROSS-REFERENCE TO RELATED APPLICATIONS

The current application claims priority to U.S. Provisional PatentApplication No. 62/818,052 filed Mar. 13, 2019 and entitled “MAGNETICPARTICLE ACTUATION,” the contents of which are hereby incorporated byreference in their entirety.

BACKGROUND

Magnetic nanoparticles (MNPs) can be utilized in the diagnosis andtreatment of certain medical conditions. Exemplary treatments caninclude tissue ablation, drug/payload delivery (e.g., carried by MNPs),hyperthermia (the heating of tissue, typically to kill canceroustissues), the use of MNPs as a potentiator or adjuvant for othertherapies such as chemo and/or radiation therapy, etc. These treatmentscan be performed in part by “actuating” the MNPs causing local heating,breaking apart of aggregate structures (as with drug/payload delivery),etc. Actuation may be performed by applying an RF field to the MNPswithin the patient.

SUMMARY

Systems, methods, and computer program products are disclosed that mayallow the generating a of magnetic field with a magnet system, where themagnetic field includes a field-free region at least partially matchinga target region. Also, an excitation field may be applied with anexcitation system to cause actuation of magnetic nanoparticles in anactuation region. In some embodiments, at least partially matching thefield-free region to the target region can include enclosing the targetregion within the field-free region, conforming the field-free region tothe target region, or avoiding overlap with a region to avoid.Additional target region(s) may be determined during a process ofcovering an entire therapeutic region to be actuated during a treatment,while avoiding actuation of a region to avoid.

Also, the at least partial matching of the field-free region to thetarget region can be performed by translating the field-free region tothe target region, scaling the field-free region, changing a shape ofthe field-free region, or rotating-the field free region. Further, theat least partial matching of the field-free region to the target regioncan include causing mechanical movement of one or more magnets ormagnetic materials in the magnet system to translate, scale, rotate, orchange the shape of the field-free region. The magnet system can alsoinclude one or more electromagnets and the at least partial matching offield-free region to the target region can be based at least oncontrolling current(s) in the one or more electromagnets.

An excitation system can apply the excitation field, for example, bygenerating the excitation field in a manner that changes the actuationregion. Generating of the excitation field can be performed throughmultiple independently controllable RF coils to enable changing theactuation region along multiple axes. Also, the multiple independentlycontrollable RF coils can allow selection of an RF vector along whichthe actuation region can be changed through specifying currents throughthe multiple independently controllable RF coils. The generating of theexcitation field can also be performed through at least one spatiallyinhomogeneous RF coil.

In some embodiments, an image of the patient can be obtained and thefield-free region can be located and/or shaped to approximately coincidewith the target region identified based at least on the image. In otherembodiments, a treatment plan for the target region can be received,with the treatment plan specifying the actuation to be delivered to themagnetic nanoparticles. One or more images of the patient can begenerated or received, and the actuation can be automatically modifiedbased at least on a change in the patient, a change in the magneticnanoparticles, or a change in a predicted dose as determined from theone or more images. The excitation field can be applied to perform themodified actuation. Also, a magnetic particle imaging signal can bereceived simultaneously with application of the excitation field. Anactuation dose can be determined based at least on a calculation usingthe magnetic particle imaging signal and the excitation field can bemodified based at least on the actuation dose.

In some embodiments, a magnetic particle imaging system can include amagnet system configured to generate a magnetic field that includes afield-free region, an excitation system configured to generate anexcitation field to cause actuation of magnetic nanoparticles in anactuation region, a control system configured to control the magnetsystem to create a field-free region at least partially matching atarget region. The magnetic particle actuating system can also includean RF shield disposed between a portion of the excitation system and aportion of the magnet system to reduce interference of the excitationsystem during the generation of the excitation field.

Implementations of the current subject matter can include, but are notlimited to, methods consistent with the descriptions provided herein aswell as articles that comprise a tangibly embodied machine-readablemedium operable to cause one or more machines (e.g., computers, etc.) toresult in operations implementing one or more of the described features.Similarly, computer systems are also contemplated that may include oneor more processors and one or more memories coupled to the one or moreprocessors. A memory, which can include a computer-readable storagemedium, may include, encode, store, or the like, one or more programsthat cause one or more processors to perform one or more of theoperations described herein. Computer implemented methods consistentwith one or more implementations of the current subject matter can beimplemented by one or more data processors residing in a singlecomputing system or across multiple computing systems. Such multiplecomputing systems can be connected and can exchange data and/or commandsor other instructions or the like via one or more connections, includingbut not limited to a connection over a network (e.g., the internet, awireless wide area network, a local area network, a wide area network, awired network, or the like), via a direct connection between one or moreof the multiple computing systems, etc.

The details of one or more variations of the subject matter describedherein are set forth in the accompanying drawings and the descriptionbelow. Other features and advantages of the subject matter describedherein will be apparent from the description and drawings, and from theclaims. While certain features of the currently disclosed subject matterare described for illustrative purposes in relation to particularimplementations, it should be readily understood that such features arenot intended to be limiting. The claims that follow this disclosure areintended to define the scope of the protected subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, show certain aspects of the subject matterdisclosed herein and, together with the description, help explain someof the principles associated with the disclosed implementations. In thedrawings,

FIG. 1A is a diagram illustrating a simplified perspective of anexemplary coil system and FFR in accordance with certain aspects of thepresent disclosure,

FIG. 1B is a diagram illustrating an exemplary magnetization curveillustrating a threshold for defining a FFR in accordance with certainaspects of the present disclosure,

FIG. 2 is a diagram illustrating an exemplary at least partial matchingof a FFR to target regions in a patient in accordance with certainaspects of the present disclosure,

FIG. 3 is a diagram illustrating an exemplary enclosing of a targetregion with a FFR in accordance with certain aspects of the presentdisclosure,

FIG. 4 is a diagram illustrating an exemplary conforming of a FFR with atarget region in accordance with certain aspects of the presentdisclosure,

FIG. 5 is a diagram illustrating an exemplary of a FFR not overlappingwith a region to avoid in accordance with certain aspects of the presentdisclosure,

FIG. 6 is a diagram illustrating an exemplary translating of a FFR inaccordance with certain aspects of the present disclosure,

FIG. 7 is a diagram illustrating an exemplary scaling of a FFR inaccordance with certain aspects of the present disclosure,

FIG. 8 is a diagram illustrating an exemplary shaping of a FFR inaccordance with certain aspects of the present disclosure,

FIG. 9 is a diagram illustrating an exemplary rotating of a FFR inaccordance with certain aspects of the present disclosure,

FIG. 10 is a diagram illustrating an exemplary actuation of additionaltarget regions in accordance with certain aspects of the presentdisclosure,

FIG. 11 is a diagram illustrating an exemplary continuous activation oftarget regions in a patient in accordance with certain aspects of thepresent disclosure,

FIG. 12 is a diagram illustrating an exemplary actuation of an entirepatient except for a region to avoid in accordance with certain aspectsof the present disclosure,

FIG. 13 is a diagram illustrating an exemplary process for FFR matchingto a target region and actuation of magnetic nanoparticles in accordancewith certain aspects of the present disclosure,

FIG. 14 is a diagram illustrating a simplified top view of an exemplarymagnetic particle actuating system with a first magnet set in accordancewith certain aspects of the present disclosure,

FIG. 15 is a diagram illustrating an exemplary generation of a FFR inthe magnetic particle actuating system of FIG. 14 in accordance withcertain aspects of the present disclosure,

FIG. 16 is a diagram illustrating an exemplary changing the size of aFFR in the magnetic particle actuating system of FIG. 14 in accordancewith certain aspects of the present disclosure,

FIG. 17 is a diagram illustrating an exemplary translating and changingthe size of a FFR in the magnetic particle actuating system of FIG. 14in accordance with certain aspects of the present disclosure,

FIG. 18 is a diagram illustrating a simplified front view of anexemplary magnetic particle actuating system adding a second magnet setin accordance with certain aspects of the present disclosure,

FIG. 19 is a diagram illustrating a simplified front view of anexemplary Halbach array in accordance with certain aspects of thepresent disclosure,

FIG. 20 is a diagram illustrating a simplified front view of translateda Halbach array in accordance with certain aspects of the presentdisclosure,

FIG. 21 is a diagram illustrating a simplified front view of anexemplary magnetic particle actuating system combining permanentmagnets, non-permanently magnetized magnetic materials, andelectromagnets in accordance with certain aspects of the presentdisclosure,

FIG. 22 is a diagram illustrating a simplified front view of anexemplary magnetic particle actuating system with a magnet translated tochange the shape of the FFR in accordance with certain aspects of thepresent disclosure,

FIG. 23 is a diagram illustrating an exemplary application of an RFfield on a vector along an X axis, which during actuation rapidlyoscillates an FFR along the vector path, leading to an actuation regionthat encompasses the full volume impinged by the FFR during actuation,in accordance with certain aspects of the present disclosure,

FIG. 24 is a diagram illustrating an exemplary application of an RFfield on a vector along a Y axis, which during actuation rapidlyoscillates an FFR along the vector path, leading to an actuation regionthat encompasses the full volume impinged by the FFR during actuation,in accordance with certain aspects of the present disclosure,

FIG. 25 is a diagram illustrating an exemplary application of an RFfield on a vector with components along an X axis and Y axis, whichduring actuation rapidly oscillates an FFR along the vector path,leading to an actuation region that encompasses the full volume impingedby the FFR during actuation, in accordance with certain aspects of thepresent disclosure,

FIG. 26 is a diagram illustrating a side view of an exemplary wire loopin accordance with certain aspects of the present disclosure,

FIG. 27 is a diagram illustrating a side sectional view of an exemplarymagnetic particle actuating system including a swappable cassette inaccordance with certain aspects of the present disclosure,

FIG. 28 is a diagram illustrating an exemplary open-loop workflow inaccordance with certain aspects of the present disclosure,

FIG. 29 is a diagram illustrating an exemplary closed loop workflowusing images for actuation feedback in accordance with certain aspectsof the present disclosure, and

FIG. 30 is a diagram illustrating an exemplary closed loop workflowusing real-time dosimetry for actuation feedback in accordance withcertain aspects of the present disclosure.

DETAILED DESCRIPTION

The application of an RF field to magnetic nanoparticles (MNPs) can beused to induce changes in a subject or treat patient conditions, forexample, macroscopically heating a treatment site in a patient, breakingapart/physically changing MNPs or MNP aggregate constructs to deliver adrug to a treatment site, or stimulating differential gene activationthrough microscopic or macroscopic heat generation. Using MNPs togenerate heat in tissues can be an effective treatment for some cancers.Specifically, MNPs located at a tumor can be heated in a controlledmanner to cause or assist with the killing of cancerous tissue.

It is believed that the heat generated by excitation of MNPs is causedby the combined effect of hysteresis (resistive heating from inductioncaused by reorienting the MNPs magnetic dipole), the Neel effect(heating due to induced currents resulting from supermagnetism), andfrictional heating (changing the physical alignment of MNPs, where theenergy delivered to the moving MNPs cause a frictional heating of thenearby tissue).

The present disclosure expands on the general actuation art, in part,through the utilization of magnetic Field Free Region concepts, whichcan assist in the localization of where MNP actuation will take place.Spatial localization can be affected by the nonlinear magneticsaturation phenomena of MNPs. The magnetization or M-H curve of manyMNPs is “S-shaped” as shown in FIG. 1B because they exhibit saturation.Higher applied field strengths thus achieve less and less increase inthe magnetization of an MNP, eventually plateauing, such that furtherincreases in field magnitude yield no detectable change in magnetizationmagnitude. Therefore, with the application of a strong spatial gradientfield, MNPs within some small region can be unsaturated (this region maybe referred to herein as the “field-free region” or FFR). MNPs outsideof this FFR are essentially locked in place and therefore analternating-current (AC) RF field can preferentially actuate (e.g., leadto heat generation) particles in the vicinity of the FFR. For actuationapplications that do not necessarily involve macroscopic heatgeneration, e.g., drug delivery or gene activation, this spatiallocalization concept remains true, although the physical details willdiffer.

In the most general sense, an FFR is a region of lower magnetic fieldmagnitude distinguished from a surrounding or adjacent region of highermagnetic field magnitude. An FFR can be established at a certainlocation through the creation of a magnetic null. One example of thecreation of a FFR 110 is shown in FIG. 1A, which illustrates two coils120 where currents with equal magnitude but flowing in oppositedirections in the coils generate opposing magnetic fields 130. An FFR isformed surrounding the region between the coils where the magnetic fieldtransitions through zero field strength.

The overall shape and structure of an FFR is determined by theorientation and strength of magnets and magnetic materials generating amagnetic field with a nonzero spatial gradient at least somewhere in avolume of interest. Complex or asymmetric orientations of magnets andmagnetic materials can generate complex or asymmetric FFRs asillustrated in the example shown in FIG. 22. The magneticcharacteristics of an MNP of interest, e.g., to be actuated, can be usedto further determine specific sizing and contours of an FFR. Forexample, in the field of magnetic particle imaging, a magnetic fieldgradient and MNP M-H curve can define a point-spread function (PSF) thatdefines how well an FFR spatially localizes signals from an MNP. Variousmetrics such as the full-width-at-half-maximum (FWHM) of the PSF orcontours created by applying thresholds to the magnitude of the magneticfield in a volume can be used to identify the FFR shape (e.g., the FFRis the region of space where the magnetic field magnitude is less thansome value). For example, as illustrated in FIG. 1B, in someembodiments, the threshold for the FFR can be an applied field strength,or some fraction thereof, associated with inflection in the M-H curvefor a MNP due to magnetic saturation. Depending on the M-H curve of anMNP, an inflection point may be identified in the range of 1-100 mT, forexample. In other embodiments, a threshold may be determined by theapplied field strength at which the MNP achieves substantialmagnetization saturation (e.g., 95% or 99% of Msat, the maximum magneticsaturation for an MNP, as illustrated in FIG. 1B). In other embodiments,the threshold may be the field amplitude where 80%, 70%, 60%, 50%, 40%,30%, 20%, or 10% Msat is achieved, or essentially no magnetic field. Inother embodiments, the threshold may be chosen as some absolute fieldvalue that pertains to an actuation physics.

While the term field “free” region is a bit of a misnomer (and while anabsolute delineation of an FFR can be elusive, as seen from thediscussion above), for the purpose of the present disclosure, an FFR isgenerally a region of low magnetic field adjacent to or surrounded by aregion of higher magnetic field. Furthermore, regardless of how fieldthresholds to identify contours of interest are chosen, the shape of anFFR is determined by the spatial structure of the total applied magneticfield, which is fully determined by arrangements and strengths ofmagnets and magnetic materials.

As used herein, embodiments of a field-free region (FFR) may beoptionally described as a field-free point (FFP) or a field free line(FFL). A field free point or FFP refers to an approximately ellipticalregion of low magnetic field. A field-free line or FFL is generally anFFR elongated greatly along one axis, having a length and a thickness,where the magnetic field is similarly low. As used herein, a “field-freeregion” is understood to account for the reality that it may not be aperfectly straight line, a perfect ellipsoid, nor completely absent amagnetic field, but that such are often goals in the creation of an FFR.Also, as discussed further herein, the FFR need not have a regulargeometric shape and can instead be shaped or formed to have an irregularshape or other shape as called for by a particular application and asgenerated by a particular system/magnet configuration. As discussedbelow, flexibility in the shaping of an FFR can provide technicalbenefits for the purposes of actuating MNPs in a patient.

As used herein, a “patient” can mean any living or nonliving object thatmay contain the magnetic nanoparticles. A patient can be, for example, ahuman, or an animal subject. In other cases, an inanimate object thatmay contain magnetic nanoparticles for calibration or research purposesmay be referred to as a patient.

In most applications of the present disclosure, it can be a goal todeposit energy into a target region (e.g., a tumor) where there may bean accumulation of magnetic nanoparticles. Often this will be for thepurpose of applying a therapy to a patient. Accordingly, as used herein,a “target region” is generally a region intended for treatment. Theremay be an accumulation of magnetic particles in regions that are notintended to be actuated (e.g., MNPs that have accumulated in a patient'shealthy liver). As used herein, such regions are referred to as“region(s) to avoid.” Furthermore, different target regions may bedistinguished from each other at least to apply different degrees orextents of actuation.

In one embodiment, target regions can be identified in MPI images takenof the subject, or alternatively using an imaging modality that can beco-registered with the magnet particle actuator system (e.g., throughthe use of common fiducial markers). Target regions for actuation may beidentified manually by a user or automatically using an algorithm. Acomputerized program can then calculate and execute optimal actuationprocedures.

In some embodiments, the procedure can include a discrete number ofactuation steps to actuate target regions. In other embodiments,continuously varying FFR trajectories are prescribed, or somecombination of both.

In certain embodiments of the present disclosure, it can be a goal tomatch an FFR with a target region. As described further below, FFRs maybe translated, scaled, and reshaped using aspects of a magnet system.For example, an FFR shape may be linearly and isotropically scaled inall dimensions by increasing or decreasing the distance between certainmagnets. The same can be accomplished by symmetric radial expansion orshrinking of magnet arrangements. In some cases, simple scaling of anFFR will accomplish the desired matching of the FFR to a target region.In other cases, reshaping of the FFR will be required. As will bediscussed, myriad FFR shapes can be created by independently translatingmagnetic materials and/or changing currents in electromagnets includedwithin the magnet system.

As described in further detail below, the present disclosure providessystems, methods and computer software that enable modification of anFFR in order to better approximate a desired actuation region. Toprovide for actuation of MNPs, embodiments of the present disclosure caninclude generating a magnetic field with a magnet system, the magneticfield including a field-free region at least partially matching a targetregion. To then actuate the MNPs, an excitation field can be appliedwith an excitation system to cause actuation of magnetic nanoparticlesin an actuation region.

One example of at least partial matching of FFRs to target regions isillustrated in FIG. 2. Here, a patient 210 (in this case, a rat) isillustrated on the left as having target regions 220, 230 and region toavoid 240. On the upper right, FFR 250 is illustrated as enclosingtarget region 220. This allows a localized actuation of MNPs in targetregion 220. Then, as shown on the lower right, FFR 250 can be moved andmodified to enclose the other target region 230. In this way, one ormore target regions can be selected for actuation and treatment byplacement and shaping of an FFR, while not actuating a region to avoid.

When “at least partially matching a target region” with an FFR, it iscontemplated that the intended degree of matching may take intoaccount 1) the fact that excitation fields will rapidly alter thelocation and possibly shape of the FFR in an oscillatory fashion. Asdiscussed herein, an actuation region can be the total volume the shapedFFR impinges during excitation, and 2) the fact that having theactuation region match the target region is a primary consideration inactuation. Thus, an FFR may be created that does not entirely match atarget region statically, but when combined with the effects of theexcitation field the actuation region will nonetheless more accuratelymatch the target region.

The present disclosure contemplates numerous ways in which the FFR maybe at least partially matched to the target region. In someimplementations, at least partially matching the field-free region tothe target region can include enclosing the target region within thefield-free region. One example of enclosing a target region isillustrated in FIG. 3, showing FFR 310 enclosing target region 320 suchthat MNPs in the entire target region can potentially be actuated fortreatment.

In some implementations, at least partially matching the field-freeregion to the target region can include conforming the field-free regionto the target region. One example of conforming an FFR to a targetregion is illustrated in FIG. 4, showing an FFR 410 that has been shapedto conform closely with target region 420, allowing a highly efficientactuation of MNPs at the target region. “Conforming,” as used herein,can mean replicating the shape of the target region, but more typicallyis intended to mean approximating the target region with some excessmargin (as shown in FIG. 4). For example, in various embodiments, theFFR may exceed the target region by 5%, 10%, 20%, etc. or,alternatively, by 2 mm, 3 mm, 4 mm, etc.

Due to limitations of the system or the anatomy and treatment needs ofthe patient, it may not always be possible to provide full coverage of atarget region by the FFR. Therefore, in some implementations, at leastpartially matching the field-free region to the target region caninclude avoiding overlap with a region to avoid. One example ofenclosing a target region is illustrated in FIG. 5, showing FFR 510enclosing a portion of the target region 520, while the remainingportion 540 of the target region is unable to be enclosed by this FFRdue to the shape of nearby region to avoid 530. The present disclosurecontemplates that the enclosing, conforming, and avoiding of overlapwith a region to avoid can be achieved in part by utilizing changes inthe FFR caused by the excitation field.

The types of matching described above can be implemented according toany combination of operations for generating, shaping, moving, etc., ofthe FFR. For example, in some implementations, at least partiallymatching the field-free region to the target region can includetranslating the field-free region to the target region. One example oftranslating the FFR is illustrated in FIG. 6. The top portion of FIG. 6illustrates a patient where FFR 610 is not in position to cover targetarea 620. In the bottom portion of FIG. 6, the FFR has been translatedsuch that it covers the target area.

In some implementations, at least partially matching the field-freeregion to the target region can include scaling the field-free region.One example of scaling the FFR is illustrated in FIG. 7. The top portionof FIG. 7 illustrates a patient where FFR 710 is too small to cover thetarget area 720. In the bottom portion of FIG. 7, FFR 710 has beenscaled to enlarge the FFR such that it covers target area 720.

In some implementations, at least partially matching the field-freeregion to the target region can include changing the shape of thefield-free region. One example of changing a shape of the FFR isillustrated in FIG. 8. The top portion of FIG. 8 illustrates a patientwhere FFR 810 covers target area 820 but could result in actuation ofMNPs that are outside the target area. In the bottom portion of FIG. 8,FFR 810 has been changed in shape to improve the matching of the FFR totarget region 820.

In some implementations, at least partially matching the field-freeregion to the target region can include rotating the field-free region.One example of rotating the FFR is illustrated in FIG. 9. The topportion of FIG. 9 illustrates a patient where FFR 910 is generallyshaped to target region 920, however it is still unable to efficientlycover the target region. In the bottom portion of FIG. 9, FFR 910 hasbeen rotated such that the matching of the target area 920 is improved.

An actuation region is a region where MNPs are actuated. As used herein,an “actuation region” is typically of the same extent or larger than thetarget region. In some embodiments, the actuation region can be theregion impinged by the shaped FFR during actuation. This can beinfluenced by a statically (i.e., not considering RF excitation effects)matched FFR shape and location and also by the path an RF excitationfield translates the FFR through during actuation (along with anyfurther shaping—as would happen with an inhomogeneous RF field).

Implementations of the current subject matter can include determiningadditional target region(s) during a process of covering an entiretherapeutic region to be actuated during a treatment, while avoidingactuation of a region to avoid. In some treatments, it may be necessaryor desirable to treat an entire therapeutic region in a manner thatrequires determining multiple target regions.

In one simple example, as illustrated in FIG. 10, a patient can havemultiple target regions 1010, 1020. Target regions can be distinguishedby physical separation and/or different actuation extents or protocols.The additional target regions can then be actuated in series as shown inthe right portion of FIG. 10 where one target region 1010 is actuatedbased on location of FFR 1030 and then the other target region 1020 canbe actuated after FFR 1030 has been moved and reshaped.

In some cases, continuous movement of an FFR may be used in conjunctionwith FFR shaping to achieve more complex desired actuation procedures.One example of continuously moving an FFR to allow actuation of acomplex target shape is illustrated in FIG. 11. The continuous movementof FFR 1110 is illustrated by the snapshots of the FFR position andshape at a number of times. The continuous manner of actuating wouldthen result in the envelope 1120 shown, which would correspond to anactuation region having the complex shape shown and avoiding actuationin a region to avoid 1130. Accordingly, some implementations of thecurrent subject matter can allow for actuation of regions having complexshapes by performing actuating of additional target regions in acontinuous manner.

By moving an FFR through a defined volume, actuation regions can beformed with more complex shapes and potentially larger total volumes ofactuation than that which can be accomplished with a shaped, but fixedmean FFR location. Since the FFR shape can be modified while moving theFFR, this makes it possible to draw more precise treatment contours(e.g., to conform the actuation region to a tumor shape, or when nearingregions to avoid).

Furthermore, depending on the type and degree of actuation application,the combination of FFR shaping and dynamic movement can be leveraged tonavigate an optimal tradeoff space between continual actuation/residencetime and overall actuation coverage. For example, in some cases it willbe more desirable to constantly and completely actuate a subregion of atarget region for a period of time, then move to another subregion, andso forth. In other cases, it may more desirable to scan from subregionto subregion and back and forth whereby actuation of all subregions iscompleted after some number of such cycles.

Continuous movement of an FFR, as described above, is distinguished fromdynamic RF excitation trajectories (discussed further below) at least byhaving lower temporal bandwidth and potentially higher power. As such,this dynamic movement of the FFR may contribute little or nothing toactuation directly, only by moving the RF-oscillating FFR through targetvolumes. In this manner, the FFR can be moved more slowly across alarger volume than that possible by changing RF excitation parametersdynamically. In some embodiments, dynamic FFR movement can be providedby electromagnets in the magnet system with a temporal bandwidth lessthan or equal to 1 kHz.

Other implementations can include having the entire therapeutic regionto be actuated as essentially the entire patient, other than a region toavoid. A simplified example of such is depicted in FIG. 12. Here, thepatient has a region to avoid 1210, shown by the dark region in thecenter of the patient. Systems disclosed herein can apply multiple orcontinuous actuations to cover the entire patient (depicted here byshading throughout the patient). In one implementation, large FFRs 1220can be used for large actuation regions that may cover large sections(or the majority) of the patient while the region(s) to avoid can avoidbeing actuated by using smaller FFRs 1230 (illustrated in FIG. 12 bydashed outlines proximate the region to avoid).

When the term “essentially the entire patient” is used herein, it iscontemplated that such could refer to just a significant portion of apatient—for example, essentially the entire patient located within thescanner (in the case where the scanner may not fit the whole body of thepatient). Similarly, it may refer to a macroscopic section of a patient,for example, actuation of a fraction (e.g., half, quarter, etc.) of thepatient (e.g., upper abdomen or lower abdomen).

It should also be noted that when the present disclosure describes“avoiding” a region, such does not require that there be absolutely zeroactuation in such a region but rather that an effort is made tosubstantially limit actuation in the region to avoid. As is understood,field-free regions and actuation regions do not necessarily have sharpboundaries and therefore a small amount of actuation may occur in aregion trying to be avoided.

Any combination of the disclosed methods of shaping the FFR to at leastpartially match the target region and actuating MNPs in an actuationregion can be implemented by computer software and corresponding magnetsystems, excitation systems, and control systems as described herein.For example, as illustrated in FIG. 13, at 1310, computer operations caninclude generating a magnetic field with a magnet system, the magneticfield including a field-free region at least partially matching a targetregion.

At 1320, an excitation field can be applied with an excitation system tocause actuation of magnetic nanoparticles in an actuation region.

Other embodiments can include additional operations, for example, at1330, the operations can further include determining additional targetregion(s) during a process of covering an entire therapeutic region tobe actuated during a treatment, while avoiding actuation of region(s) toavoid.

Also, the operations can optionally include, at 1340, actuatingadditional target regions in series, at 1350, actuating additionaltarget regions in a continuous manner, or at 1360, causing an entiretherapeutic region to be actuated to be essentially the entire patientother than the region to avoid.

To localize RF actuation of nanoparticles with high spatial resolutionin a patient, one or more FFRs can be generated using magnet systems asdisclosed herein. Implementations of the magnet system can be configuredto change the size, shape, rotation and/or location of the one or moreFFRs, as previously discussed.

FIG. 14 illustrates one example of such a magnetic particle actuatingsystem. The magnetic particle actuating system can include a magnetsystem configured to generate a magnetic field that includes an FFR. Themagnet system can include magnetic materials and/or electromagnets, witha first set of magnets 1410 shown in FIG. 14. As used herein, “magneticmaterials” include permanently magnetized materials (permanent magnets),non-permanently magnetized materials (e.g., ferromagnetic materials suchas iron, steel, and nickel), or ferrimagnetic materials (e.g., yittriumiron garnet, aluminum, cobalt, nickel, etc.). As used herein, the term“magnet” can refer to permanent magnets or electromagnets.

The magnet system can also include associated mechanical supportstructures and one or more control systems that can encompass anymechanical/electrical mechanisms for translating, rotating, moving, oroperating of any of the components of the magnet system or excitationsystem. FIG. 14 illustrates simplified representations of stage systemsfor moving one or more components of the magnet system. For example, asdiscussed further below, stage systems can include an X-axis stage 1420and/or a Y-axis stage 1430, as well as other stages for furthertranslations or rotation of components of the magnet system.

A control system 1440 can be configured to control the magnet system tocreate a field-free region at least partially matching a target region.The at least partially matching of the field-free region to the targetregion can include causing mechanical movement of one or more magnets ormagnetic materials in the magnet system to translate, scale, rotate, orchange the shape of the field-free region. The control system can befurther configured to control the magnet system to cause the field-freeregion to enclose a target region, conform to the target region, oravoid overlap with a region to avoid.

Additionally, the control system can be configured to determineadditional target region(s) for a process of covering an entiretherapeutic region to be actuated during a treatment, while avoidingactuation of a region to avoid, to actuate the additional target regionsin series, to actuate the additional target regions in a continuousmanner, or to actuate essentially an entire patient, other than theregion to avoid.

To provide support for and positioning of the patient in the magneticactuation system, a patient couch 1450 can be provided. The patientcouch can allow for movement of the patient into the bore of themagnetic actuation system where the FFR will be generated. As furtherdiscussed below, the patient couch can be connected to the controlsystem for controlling the relative position between the patient (andthe target regions therein) and the FFR.

Other elements illustrated in FIG. 14 and discussed herein includecomponents 1460 of an RF excitation system and shielding 1470 betweenthe RF excitation system and the magnet system. Optionally, sensors 1480such as thermal probe sensors or other devices configured to monitor theeffects of MNP actuation can be included in the magnetic actuationsystem.

As shown in FIGS. 15-17, the magnet system can include a first set ofmagnets 1410 on either side of the field-free region. This first set ofmagnets can be controlled to, for example, translate or change the shapeof the FFR. FIG. 15 illustrates a simplified FFR 1510 locatedapproximately at the center of the magnetic actuation system and createdby the pair of magnets 1410 that are of equal magnetic strength.

FIG. 16 illustrates a simplified representation of the effect oftranslating outward both magnets of the first set of magnets. Here, FFR1510 increases in size due to the reduced gradient field strengthproduced by the magnetic actuation system. When only one magnet istranslated, as illustrated in FIG. 17 by the left magnet having movedoutward, this causes two effects on the FFR. First, FFR 1510 increasesin size from the increased separation between the magnets, similar tothe increase in size shown in FIG. 16. Second, FFR 1510 translates tothe left due to the change in the location of the magnetic null betweenthe two magnets. This simplified example illustrates how the movement ofmagnets can cause multiple effects in the sizing and location of theFFR.

Accordingly, the at least partial matching of the field-free region tothe target region can include independently controlling at least one ofa first set of magnets to translate along a first axis (shown in FIGS.15-17 as being the X axis). The translation can be implemented by afirst magnet stage system configured to independently translate at leastone of the first set of magnets along the first axis. In this way, thecontrol system can then be further configured to control at least one ofthe first set of magnets to translate along the first axis as part ofthe at least partial matching of the field free region to the targetregion.

Furthermore, the first magnet stage system can be configured toindependently translate along a second axis (e.g., up and down along theY axis). Accordingly, the control system can be further configured tocause mechanical translation of the first set of magnets along a secondaxis as part of the at least partial matching of the field-free regionto the target region.

As noted, the system can also include a patient couch. The controlsystem can be further configured to control reorientation of the patientcouch as part of the at least partial matching of the field-free regionto the target region. As shown in FIGS. 14-17, the patient couch may beintroduced into a magnet-free region (e.g., the bore) with a translationmechanism such as a linear stage. Additionally, the magnet system and/orthe translation mechanism(s) can adjust the relative positioning betweenthe patient and one or more FFRs to, for example, improve the matchingof the FFR for actuation of MNPs.

Additional control over the shape and placement of the FFR can beachieved by including additional magnets, for example, as in theimplementation illustrated in FIG. 18 showing a simplified front view ofthe magnetic particle actuation system. In this implementation, themagnet system further includes a second set of magnets 1810 on eitherside of field-free region 1820 (e.g., above and below the center of themagnetic particle actuation system). As shown in FIG. 18, first set ofmagnets 1410 and second set of magnets 1810 can be disposed outside bore1830. There can also be a second magnet stage system configured toindependently translate at least one of the second set of magnets alonga second axis (e.g., up and down along the Y-axis as shown in FIG. 18).The control system can be further configured to control at least one ofthe second set of magnets to translate along the second axis as part ofthe at least partial matching of the field-free region to the targetregion. This second set of magnets allows additional degrees of freedomfor manipulating the shape or location of the FFR, similar to what waspreviously shown in FIGS. 14-17.

Still further manipulation of the FFR can be achieved by, for example,inclusion of an array of radially oriented magnetic materials. Inparticular, FIG. 19 shows one example of a Halbach array 1910 havingmagnetic materials 1920 (e.g., a generally circularly oriented array ofmagnets). In some implementations, a Halbach array can include permanentmagnets, electromagnets, and/or ferromagnetic material such as iron toassist with forming a desired FFR. Additionally, as illustrated in FIG.20, the Halbach array can be translated similar to the previouslydescribed magnet sets. And similar to the previously described magnetsets, such translation can cause a translation of the FFR.

In yet other implementations, the control system can be furtherconfigured to move one or more of the magnetic materials to a specifiedradial distance as part of the at least partial matching of thefield-free region to the target region. For example, any of the magnetsof the Halbach array can be coupled to a radial drive to provide forthis independent movement. In this manner, the FFR may be shapedasymmetrically and/or multiple distinct/disjointed FFRs can be created.

In addition to being capable of independent radial movement, elements ofthe Halbach array can be configured to move together to allow, forexample, a more symmetrical change in the size and shape of the FFR (ascompared to the linear stage magnets discussed above). In someimplementations, the magnetic materials in the Halbach array can bedisposed in a circular configuration having a diameter. Accordingly, thecontrol system can be further configured to control the plurality ofmagnetic materials to move radially to change the diameter of theHalbach array as part of the at least partial matching of the field-freeregion to the target region.

In some implementations, the magnet system can include one or moreelectromagnets and the at least partially matching the field-free regionto the target region can be based at least on controlling current(s) inthe one or more electromagnets. In systems comprising one or moreelectromagnets, the electromagnets may be used to electronically shiftthe location/shape of the FFR in place of, or in combination withmechanical movement of the magnets.

The above magnet systems can be combined in various geometries andlocations to provide high-resolution, multi-dimensional control over theFFR. For example, as shown by the embodiment illustrated in FIG. 21, themagnet system can include one or more permanent magnets 2110, one ormore magnetic materials 2120, and one or more electromagnets 2130. Here,the different magnet types are arranged at different radial distancesfrom the center of the bore. However, this is intended to be an exampleonly and as such the location, number, and radial order of any of themagnets can be varied.

The control system can be further configured to cause mechanicalmovement of the one or more permanent magnets and cause mechanicalmovement of one or more magnetic materials that is not permanentlymagnetized and control current(s) in the one or more electromagnets totranslate, scale, rotate, or change the shape of the field-free region.FIG. 22 illustrates an example of how just a simple translation of sucha magnet system can result in a complex FFR. The upper left illustrationin figure FIG. 22 shows a simplified arrangement of six magnets 2210disposed symmetrically around bore 1830. Below it, is a simplifiedillustration of magnetic field lobes 2220 generated by such magnets. Inthe center of the lower left illustration is a depiction of a resultantFFR 2230 having a circular shape in the X-Y plane (due to the symmetryof the magnet configuration). The upper right illustration shows the topmagnet 2250 translated radially inward. Below that illustration is adepiction of the resultant magnetic field lobes 2220 and new FFR 2250,having a significantly more complex shape.

Active excitation, energy deposition, or actuation of magneticnanoparticles can be achieved via radiofrequency (RF) fields. RF coilscan be designed to generate the desired fields with a geometry specifiedin terms of the coil sensitivity and the theory of reciprocity. In someembodiments, RF coils will be designed to provide a substantiallyspatially homogeneous field over some field-of-view (FOV).

While an FFR created by the magnet system (as described above) canprovide a powerful actuation-localization mechanism, RF coil sensitivityprofiles can also be used to shape energy deposition. The combination ofspecialized RF coil sensitivity localization and FFR localization canthus provide an unprecedented degree of spatial targeting in RFactuation.

An excitation field can be applied through an excitation system that caninclude one or more RF coils. In one implementation, the magneticparticle actuating system can include a single RF coil. Accordingly, thecontrol system can be further configured to generate the excitationfield with the single RF coil. In other implementations, the excitationsystem can include at least one spatially inhomogeneous RF coil and thecontrol system can be further configured to generate the excitationfield utilizing the at least one spatially inhomogeneous RF coil.

In other embodiments, the excitation system can include multiple RFcoils that can be independently controllable. For example, a solenoid RFcoil circumscribing the magnet-free region may provide excitation with afield vector oriented perpendicular to the circular cross-section of thecoil and RF saddle coils may provide excitation with a field vectororiented along the remaining perpendicular spatial directions. As such,the control system can be further configured to cause the excitationfield to be generated along multiple axes utilizing the multipleindependently controllable RF coils, including utilizing the solenoidalRF coil and the multiple saddle RF coils.

As described herein, the excitation field can be generated in a mannerthat changes the actuation region. In the presence of an FFR, aspatially homogeneous AC RF field will rapidly move the FFR over somedistance. Actuation of MNPs will occur along the length of the FFR path,or said another way, throughout the volume the FFR passes through overthe course of RF oscillations. Therefore, RF amplitude and vectortrajectory will also influence the spatial localization of RF actuationin addition to the means of generating and shaping an FFR (statically orwith low-frequency dynamics) and the use of spatially inhomogeneouscoils previously discussed. Furthermore, while a spatially homogeneousAC field shifts an FFR, an inhomogeneous AC field will both spatiallydistort and shift the FFR.

Simplified examples of the effect of RF vectors are illustrated in FIGS.23-25. The left portion of each figure illustrates FFR 2310, 2410, 2510.In FIG. 23, an arrow indicates an RF vector 2320 oriented along theX-axis. The right figure shows the effect of the excitation field on theactuation region. Here, because the RF vector was in the X direction,the FFR is oscillated along the X-axis such that over this time the FFRsweeps through a volume forming the shape of actuation region 2330. FIG.24 illustrates a similar effect on FFR 2410 but for an RF vector 2420 inthe Y direction. Similarly, actuation region 2430 is extended somedistance along the Y-axis. FIG. 25 illustrates yet another example whereRF vector 2520 has components in both the X and Y directions.Accordingly, FFR 2510 is oscillated in the direction of RF vector 2520based on those vector components to form actuation region 2530.

Based on the abilities of certain excitation systems disclosed herein,the control system can thus be further configured to control multipleindependently controllable RF coils to allow selection of the RF vectoralong which the actuation region is changed through specifying currentsthrough the multiple independently controllable RF coils. In someimplementations, the multiple independently controllable RF coils areconfigured to be controllable (e.g., by the control system) to change amagnitude of the RF vector through specifying currents through themultiple independently controllable RF coils. FIGS. 23-25 are onlyexemplary cases meant for illustrative purposes. In general, thegeometrical difference between the actuation region and the FFR candepend on a number of factors, such as excitation amplitude, vectordirection (shown in the figures), tracer magnetization curve, andactuation physics.

Body part-specific RF coils may be designed to make contact with thesubject and means of cooling the coil or the coil-tissue interface maybe provided. For example, a thin, water-perfused interface may separatea dedicated RF coil and a body part such as a head or a breast.

Other implementations of the current subject matter allow for atailoring of the excitation field that reaches the patient byattenuating or blocking at least some of the RF emitted from the RFcoils. For example, the magnetic particle actuating system can include apassive component. FIG. 26 illustrates one example of a passivecomponent being a wire loop that acts to attenuate the deliveredexcitation field to the target. Essentially, the wire loop shown at aparticular location along the patient causes the RF excitation fieldgenerated by RF coils 2620 to deposit a portion of their energy into thewire loop and drive a current around it. The current induced in the coilor wire loop then locally reduces the magnetic field so that less energyis transmitted to the patient in that location. In some implementations,wire loop may be a shorted wire loop that is shorted to ground orotherwise able to electrically discharge the induced current in the wireloop. The bottom of the figure shows an example representation ofamplitude 2640 of RF reaching the patient. Here, the plot shows thelocalized reduction in excitation field amplitude at the location of thewire loop, which is positioned around region to avoid 2630. It iscontemplated that the control system can be further configured to causeplacement of the passive component to shape the excitation field, forexample to avoid actuation of the region to avoid. In this way, thecontrol system can be configured to instruct the magnetic particleactuator system to move the passive component to a particular locationand/or move the patient couch to the location of the passive component.

Implementations of the magnetic particle actuating systems herein mayfurther include an RF shield disposed between a portion of theexcitation system and a portion of the magnet system (and possibly theexternal environment) to reduce interference of the excitation systemduring the generation of the excitation field. One example of such wasillustrated in FIGS. 14-17. The RF shield can be, for example, a tubemade of copper, steel, aluminum, or similarly suitable conductivematerial. In FIG. 14, distinct plates are used instead of a continuoustube/enclosed construct. In some implementations, the portion of theexcitation system inside the RF shield can include one or more RF coils.The portion of the magnet system outside the RF shield can include oneor more magnets of the magnet system. In other implementations, themagnetic particle actuating system can include one or more RF receivercoils, where the RF shield can be disposed between the one or more RFreceiver coils and the portion of the magnet system. The RF shield canbe configured to reduce interference to or from external sources (e.g.,aspects of the magnet system, AM radio, other nearby RF generatingequipment, etc.), for example, by being of sufficient thickness toshield against electromagnetic fields at an interfering frequency. Inother implementations, the RF shield can prevent detuning of thetransmit coil as the magnets are moved mechanically. In general, the RFshield can be designed with such a thickness as to block interferers ina sensitive range (e.g., encompassing the fundamental excitationfrequency and possibly some number of harmonics of the fundamentalexcitation frequency), while passing low-frequency magnetic fields,e.g., electromagnetic fields of the magnet system that translate/shapethe FFR during operation. Such low-frequency magnetic fields can be, forexample, approximately 1, 5, 10, 25, 50, 75, or 100 Hz.

The magnetic particle actuator systems disclosed herein can be usedacross a broad application spectrum. Accordingly, the desiredperformance characteristics, including desired resonant frequency,desired field strengths, and degree of spatial localization can varywidely. Therefore, the excitation system can include a swappablecassette 2710 containing at least a portion of the excitation system. Asimplified example of a system that includes the swappable cassette isillustrated in FIG. 27. The swappable cassette can be easily exchangedin magnetic particle actuating system 2720 with other swappablecassettes having different configurations of RF generating components.Portions of the excitation system in the swappable cassette can includeresonators that enable the desired performance characteristics.Resonators of different cassettes may differ in various importantmetrics such as geometry and form factor, resonant frequency, coildiameter, coil inductance, impedance, cooling strategies employed, andinteraction level with the subject (e.g., contact and non-contact).

The RF coils and elements of high-powered resonator circuits, such asthe matching capacitors, may be actively cooled. In some embodiments,thermal fluids such as water or oil may perfuse hollow coil wiring. Inother embodiments, thermal fluids bathe coils and other componentsplaced in an enclosed thermal circuit. In other embodiments, solid heatsinks may be attached with high conductivity materials to componentssuch as the matching capacitors. These heat sinks may be actively orpassively cooled. In some embodiments, various thermal mitigationmechanisms are used simultaneously. In some embodiments, the RFshielding may also be actively or passively cooled.

In some embodiments, an MPI receiver system is included in the magneticparticle actuator system. This system may include a gradiometricreceiver coil and low power receiver electronics configured to match thebandwidth of an anticipated MPI signal. For example, in someembodiments, the MPI receiver system may be sensitive to some number ofthe harmonics of the fundamental RF excitation frequency of the RFactuator system. In other embodiments, a greatly reduced bandwidth, suchas a small bandwidth around the third harmonic of the fundamentalfrequency, may be supported.

In some embodiments, the MPI receiver system, in tandem with a controland reconstruction system, is capable of generating MPI images andreporting real-time MPI signals. In some embodiments, MPI images may beused as feedback to control actuation on a timescale consistent with MPIimage acquisition and reconstruction. In other embodiments, real-timetime-domain MPI signals are supported. In some embodiments, thereal-time MPI signals from the MPI receiver system are provided to acontrol unit for presentation as real-time feedback to the user and/orused in a closed-loop feedback control of actuation. In someembodiments, MPI signals may be used alone or in combination withtemperature sensors and other monitoring signals for real-time feedbackand estimation of RF actuation dose. RF actuation dose estimations willdepend on the application and may include SAR deposition, estimatedtemperature elevation, amount of drug released, actuation of abiomolecule, etc.

In a first mode of operation, a user first takes an image of the subjectusing an MPI system, a magnetic particle actuator system in imagingmode, or any other modality that is co-registerable with the magneticparticle actuator system (e.g., MRI, CT, X-Ray, optical, photograph,anatomic database, etc.). Co-registration (of images or of themodalities themselves) may be provided by, for example, fiducial markersdistinct in both modalities, or an anatomical atlas. Target areas andany regions to avoid can be manually annotated by a user orautomatically calculated from the co-registered modality. Therapeuticplan information may be entered for each target region by a user (e.g.,Tx cassette to be used, duration of actuation, RF field strength, targetenergy deposition, target temperature, etc., and a therapeutic planningsystem will transform these inputs along with the ROI information into aspecific therapeutic plan for each target region.

To assist in therapeutic planning, energy deposition estimator tools maybe used, taking advantage of information such as the known oranticipated concentration/dose of tracer at each target region (e.g.,known from direct injection), and known MNP behavior. Furthermore, ifthe co-registered modality is an MPI system, image from the MPI systemcan be used in tandem or automatically to predict required dose/doseeffects as an MPI image intensity is linearly proportional to the localMNP concentration. When the user is finished with inputting and a finaltherapeutic plan is produced, actuation can commence in an open-loopfashion as depicted in FIG. 28.

Accordingly, in some implementations, operations can further includeobtaining, at 2810, an image of a patient, where the field-free regionis located and/or shaped to approximately coincide with the targetregion identified based at least on the image. The image can be obtainedfrom various modalities, including a magnetic particle imaging system, amagnetic resonance imaging system, an X-ray computed tomography system,an ultrasound system, or an optical fluorescent system. Then, at 2820,these images can be used for predictive dosimetry and/or therapypre-planning. At 2830, matching of the FFR to target region(s) and/oractuation can commence.

In a second mode of operation, any or all of the procedures of the firstmode of operation may apply, but a feedback loop is introduced duringactuation, as depicted in FIG. 29. In this implementation, the magneticparticle actuator system is capable of switching modes between RFactuation and MPI imaging. For example, MPI image acquisitions taking 1second-60 minutes may be periodically interspersed with RF actuationsteps and used to update actuation protocols. Updates may include takinginto account changes in MNP distribution/concentration and any resultsof actuation detectable from the MPI signal. For example, MNPs maygreatly change their MPI signal after significant heating (magneticrelaxation) or if heating/actuation disrupts an MNP carrier/deliveryconstruct (e.g., agglomerates, drug carriers, etc.).

Accordingly, in some implementations, computer operations can furtherinclude generating or receiving a treatment plan for the target region,the treatment plan specifying the actuation to be delivered to themagnetic nanoparticles.

The closed loop portion of this second mode of operation is illustratedin FIG. 29. At 2910, one or more images of the patient can be received.At 2920, these images can be used to determine a modification to theactuation based on the information in the images, the treatment plan,and/or the output of a predicted dose based on the treatment plan andthe images. For example, at 2930, the actuation can be automaticallymodified based at least on a change in the patient (e.g., patientmotion, change in temperature, change in physiological characteristicsuch as heartbeat or respiration, etc.), based on a change in themagnetic nanoparticles as determined from the one or more images (e.g.,magnetic nanoparticle distribution, release of carried drugs, etc.), orbased on a change in a predicted dose (e.g., as received from a doseprediction program utilizing the images). The excitation field then canbe applied to effect the modified actuation. Examples of modifying theactuation can include, for example, modifying a magnitude of theexcitation field or modifying a period of time of applying theexcitation field based at least on the change in the patient, magneticnanoparticles, or the predicted dose.

Given the similar physics between the magnetic nanoparticle actuationmethods described herein and magnetic particle imaging, in someimplementations, the one or more images are generated by a magneticparticle imaging system that includes the magnet system and utilizes thefield-free region. In other implementations, the images can be generatedby a magnetic resonance imaging system or an X-ray computed tomographysystem and can be co-registered to the magnet system.

In a third mode of operation, any or all of the procedures of the firsttwo modes of operation may apply (though not necessarily withoutmodification), but as depicted in FIG. 30, a second feedback loopincorporating rapid dosimetry can also be introduced during actuation.In this manner, fully simultaneous/parallel and real-time MPI (or otherimaging modality) signal information can be incorporated. Because acommon physics underlies MPI signal generation and RF actuation, a MPIsignal will exist during actuation and may be used in tight actuationfeedback loops. For example, one or more aspects of the raw MPI signalmay be calibrated to provide real-time RF energy/SAR/RF actuationestimates. Corrective or stabilizing actions may be taken by acontroller based on this real-time feedback.

Furthermore, as depicted in FIG. 30, other non-MPI based real-timesignals, such as temperature from thermal probes, may be also beprovided to the control system in real-time to further augment theclosed-loop actuation. In some embodiments, the raw MPI signal can betransformed into continuous estimations of RF actuation dose. As usedherein, use of the terms “real-time” and “simultaneous” contemplate thatthere may be some minor delay due to latency or processing overhead inthe system.

The addition of real-time actuation feedback to the process of FIG. 29is illustrated in FIG. 30. In some implementations, at 3010, a magneticparticle imaging signal can be received simultaneously with applicationof the excitation field. This is similar to the implementation discussedin reference to FIG. 29, however, the signals are generally acquired andprocessed at a faster rate (e.g., greater than 10 Hz, greater than 100Hz, greater than 1 kHz, greater than 10 kHz, greater than 100 kHz, orgreater than 1 MHz) and are not necessarily transformed into an actualimage. At 3020, these signals can be used to determine a modification tothe actuation based on the information in the images, the treatmentplan, and/or the output of a predicted dose based on the treatment planand the images. Then, at 3030, an actuation dose can be determined basedat least on a calculation using the magnetic particle imaging signal. At3040, the excitation field can be modified based at least on theactuation dose.

In the following, further features, characteristics, and exemplarytechnical solutions of the present disclosure will be described in termsof items that may be optionally claimed in any combination:

Item 1. A computer program product comprising a non-transitory,machine-readable medium storing instructions which, when executed by atleast one programmable processor, cause operations comprising:

generating a magnetic field with a magnet system, the magnetic fieldincluding a field-free region at least partially matching a targetregion; and

applying an excitation field with an excitation system to causeactuation of magnetic nanoparticles in an actuation region.

Item 2. A magnetic particle actuating system comprising:

a magnet system configured to generate a magnetic field that includes afield-free region;

an excitation system configured to generate an excitation field to causeactuation of magnetic nanoparticles in an actuation region; and

a control system configured to control the magnet system to create afield-free region at least partially matching a target region.

Item 3: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein at least partiallymatching the field-free region to the target region comprises enclosingthe target region within the field-free region.

Item 4: The magnetic particle actuating system or computer programproduct of any one of the preceding claims, wherein at least partiallymatching the field-free region to the target region comprises conformingthe field-free region to the target region.

Item 5: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein at least partiallymatching the field-free region to the target region comprises avoidingoverlap with a region to avoid.

Item 6: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the operations furthercomprising determining additional target region(s) during a process ofcovering an entire therapeutic region to be actuated during a treatment,while avoiding actuation of a region to avoid.

Item 7: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the additional targetregions are actuated in series.

Item 8: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the additional targetregions are actuated in a continuous manner.

Item 9: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the entiretherapeutic region to be actuated is essentially an entire patient,other than the region to avoid.

Item 10: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein at least partiallymatching the field-free region to the target region includes translatingthe field-free region to the target region.

Item 11: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein at least partiallymatching the field-free region to the target region includes scaling thefield-free region.

Item 12: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein at least partiallymatching the field-free region to the target region includes changing ashape of the field-free region.

Item 13: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein at least partiallymatching the field-free region to the target region includes rotatingthe field-free region.

Item 14: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the at leastpartially matching the field-free region to the target region includescausing mechanical movement of one or more magnets or magnetic materialsin the magnet system to translate, scale, rotate, or change the shape ofthe field-free region.

Item 15: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the magnet systemincludes a first set of magnets on either side of the field-free regionand the at least partially matching the field-free region to the targetregion includes independently controlling at least one of the first setof magnets to translate along a first axis.

Item 16: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the at leastpartially matching the field-free region to the target region includescausing mechanical translation of the first set of magnets along asecond axis.

Item 17: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the magnet systemincludes a second set of magnets on either side of the field-free regionand oriented along a second axis that is different than the first axis,wherein the at least partially matching further includes independentlycontrolling at least one of the second set of magnets to translate alongthe second axis.

Item 18: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the magnet systemincludes a Halbach array that includes a plurality of magnetic materialsand the at least partially matching the field-free region to the targetregion includes controlling one or more of the magnetic materials tomove to a specified radial distance from a center of the Halbach array.

Item 19: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the plurality ofmagnetic materials in the Halbach array are disposed in a circularconfiguration having a diameter, and the at least partially matching thefield-free region to the target region includes controlling theplurality of magnetic materials in the Halbach array to move radially tochange the diameter of the Halbach array.

Item 20: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the magnet systemincludes one or more electromagnets and the at least partially matchingthe field-free region to the target region is based at least oncontrolling current(s) in the one or more electromagnets.

Item 21: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the at leastpartially matching the field-free region to the target region includescausing mechanical movement of one or more permanent magnets and causingmechanical movement of one or more magnetic materials that is notpermanently magnetized, and controlling current(s) in one or moreelectromagnets to translate, scale, rotate, or change the shape of thefield-free region.

Item 22: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the at leastpartially matching the field-free region to the target region includescontrolling reorientation of a patient couch.

Item 23: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the operations furthercomprising applying the excitation field through an excitation system.

Item 24: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the operations furtherincluding generating the excitation field in a manner that changes theactuation region.

Item 25: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the generating of theexcitation field is performed through a single RF coil.

Item 26: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the generating of theexcitation field is performed through multiple independentlycontrollable RF coils to enable changing the actuation region alongmultiple axes.

Item 27: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the generating of theexcitation field is performed through a solenoidal RF coil and multiplesaddle RF coils.

Item 28: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the multipleindependently controllable RF coils allow selection of an RF vectoralong which the actuation region is changed through specifying currentsthrough the multiple independently controllable RF coils.

Item 29: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the generating of theexcitation field is performed through at least one spatiallyinhomogeneous RF coil.

Item 30: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein avoiding actuation ofthe region to avoid includes causing placement of a passive componentthat shapes the excitation field.

Item 31: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the passive componentincludes one or more wire loops.

Item 32: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the excitation systemincludes a swappable cassette in which portions of the excitation systemare included and which can be swapped out of the magnet system fordifferent performance or different therapies.

Item 33: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the operations furthercomprising obtaining an image of a patient, wherein the field-freeregion is located and/or shaped to approximately coincide with thetarget region identified based at least on the image.

Item 34: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the image is obtainedfrom a magnetic particle imaging system.

Item 35: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the image is obtainedfrom a magnetic resonance imaging system, an X-ray computed tomographysystem, an ultrasound system, or an optical fluorescence system.

Item 36: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the operations furthercomprising:

receiving a treatment plan for the target region, the treatment planspecifying the actuation to be delivered to the magnetic nanoparticles;

generating or receiving one or more images of the patient;

automatically modifying the actuation based at least on a change in thepatient, a change in the magnetic nanoparticles, or a change in apredicted dose as determined from the one or more images; and

applying the excitation field to perform the modified actuation.

Item 37: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein modifying theactuation includes modifying a magnitude of the excitation field ormodifying a period of time of applying the excitation field based atleast on the change in the patient, the magnetic nanoparticles, or thepredicted dose.

Item 38: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the one or moreimages are generated by a magnetic particle imaging system that includesthe magnet system and utilizes the field-free region.

Item 39: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the one or moreimages are generated by a magnetic resonance imaging system or an X-raycomputed tomography system, the operations further comprisingco-registering the one or more images to the magnet system.

Item 40: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the operations furthercomprising:

receiving a magnetic particle imaging signal simultaneously withapplication of the excitation field;

determining an actuation dose based at least on a calculation using themagnetic particle imaging signal; and

modifying the excitation field based at least on the actuation dose.

Item 41: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to cause the field-freeregion to enclose the target region.

Item 42: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to cause the field-freeregion to conform to the target region.

Item 43: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to cause the field-freeregion to avoid overlap with a region to avoid.

Item 44: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to determine additional target region(s) for aprocess of covering an entire therapeutic region to be actuated during atreatment, while avoiding actuation of a region to avoid.

Item 45: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to actuate the additional target regions in series.

Item 46: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to actuate the additional target regions in acontinuous manner.

Item 47: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to actuate essentially an entire patient, other thanthe region to avoid.

Item 48: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to translate thefield-free region to the target region as part of the at least partialmatching of the field-free region to the target region.

Item 49: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to scale the field-freeregion to the target region as part of the at least partial matching ofthe field-free region to the target region.

Item 50: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to change a shape of thefield-free region to the target region as part of the at least partialmatching of the field-free region to the target region.

Item 51: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the magnet system to rotate the field-freeregion to the target region as part of the at least partial matching ofthe field-free region to the target region.

Item 52: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the magnet system furthercomprising:

one or more magnetic materials; and

wherein the control system is further configured to cause mechanicalmovement of the one or more magnetic materials to translate, scale,rotate, or change the shape of the field-free region.

Item 53: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the magnet system furthercomprising:

a first set of magnets on either side of the field-free region; and

a first magnet stage system configured to independently translate atleast one of the first set of magnets along a first axis; and

wherein the control system is further configured to control at least oneof the first set of magnets to translate along the first axis as part ofthe at least partial matching of the field-free region to the targetregion.

Item 54: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the first magnetstage system is further configured to independently translate the atleast one of the first set of magnets along a second axis; and

wherein the control system is further configured to cause mechanicaltranslation of the first set of magnets along a second axis as part ofthe at least partial matching of the field-free region to the targetregion.

Item 55: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the magnet system furthercomprising:

a second set of magnets on either side of the field-free region; and

a second magnet stage system configured to independently translate atleast one of the second set of magnets along a second axis; and

wherein the control system is further configured to control at least oneof the second set of magnets to translate along the second axis as partof the at least partial matching of the field-free region to the targetregion.

Item 56: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the magnet system furthercomprising:

a Halbach array that includes a plurality of magnetic materials; and

wherein the control system is further configured to move one or more ofthe plurality of magnetic materials to a specified radial distance aspart of the at least partial matching of the field-free region to thetarget region.

Item 57: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the plurality ofmagnetic materials in the Halbach array are disposed in a circularconfiguration having a diameter; and

wherein the control system is further configured to control theplurality of magnetic materials to move radially to change the diameterof the Halbach array as part of the at least partial matching of thefield-free region to the target region.

Item 58: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the magnet system furthercomprising one or more electromagnets; and

wherein the control system is further configured to control currents inthe one or more electromagnets as part of the at least partial matchingof the field-free region to the target region.

Item 59: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the magnet system furthercomprising one or more permanent magnets, one or more magnetic materialsthat is not permanently magnetized, and one or more electromagnets; and

wherein the control system is further configured to cause mechanicalmovement of the one or more permanent magnets and cause mechanicalmovement of the one or more magnetic materials that is not permanentlymagnetized and control current(s) in the one or more electromagnets totranslate, scale, rotate, or change the shape of the field-free region.

Item 60: The magnetic particle actuating system or computer programproduct of any one of the preceding items, further comprising:

a patient couch; and

wherein the control system is further configured to controlreorientation of the patient couch as part of the at least partialmatching of the field-free region to the target region.

Item 61: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to cause the excitation system to generate theexcitation field in a manner that changes the actuation region.

Item 62: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the excitation systemincludes a single RF coil; and

wherein the control system is further configured to cause the excitationsystem to generate the excitation field with the single RF coil.

Item 63: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the excitation systemincludes multiple independently controllable RF coils; and

wherein the control system is further configured to cause the excitationsystem to generate the excitation field along multiple axes utilizingthe multiple independently controllable RF coils.

Item 64: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the excitation systemincludes a solenoidal RF coil and multiple saddle RF coils; and

wherein the control system is further configured to cause the excitationsystem to generate the excitation field utilizing the solenoidal RF coiland the multiple saddle RF coils.

Item 65: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to control the multiple independently controllable RFcoils to allow selection of an RF vector along which the actuationregion is changed through specifying currents through the multipleindependently controllable RF coils.

Item 66: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the excitation systemincludes at least one spatially inhomogeneous RF coil; and

wherein the control system is further configured to cause the excitationsystem to generate the excitation field utilizing the at least onespatially inhomogeneous RF coil.

Item 67: The magnetic particle actuating system or computer programproduct of any one of the preceding items, further comprising a passivecomponent; and

wherein the control system is further configured to cause placement ofthe passive component to shape the excitation field and avoid actuationof the region to avoid.

Item 68: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the passive componentincludes one or more wire loops.

Item 69: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the excitation systemincludes a swappable cassette containing at least a portion of theexcitation system.

Item 70: The magnetic particle actuating system or computer programproduct of any one of the preceding items, further comprising an RFshield disposed between a portion of the excitation system and a portionof the magnet system to reduce interference of the excitation systemduring the generation of the excitation field.

Item 71: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the RF shield is atube made of copper, steel, or aluminum.

Item 72: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the portion of theexcitation system is inside the RF shield and includes one or more RFcoils, and wherein the portion of the magnet system is outside the RFshield and includes one or more magnets of the magnet system.

Item 73: The magnetic particle actuating system or computer programproduct of any one of the preceding items, further comprising one ormore RF receiver coils, wherein the RF shield is disposed between theone or more RF receiver coils and the portion of the magnet system.

Item 74: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the control system isfurther configured to:

receive a treatment plan for the target region, the treatment planspecifying the actuation to be delivered to the magnetic nanoparticles;and

generate or receive one or more images of the patient;

automatically modify the actuation based at least on a change in thepatient, a change in the magnetic nanoparticles, or a change in apredicted dose as determined from the one or more images; and

apply the excitation field to perform the modified actuation.

Item 75: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the modifying of theactuation is performed by the control system that is further configuredto modify a magnitude of the excitation field or modify a period of timeof applying the excitation field based at least on the change in thepatient, the magnetic nanoparticles, or the predicted dose.

Item 76: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the magnetic particleimaging system that includes the magnet system and utilizes thefield-free region is configured to generate the one or more images.

Item 77: The magnetic particle actuating system or computer programproduct of any one of the preceding items, wherein the one or moreimages are received from a magnetic resonance imaging system or an X-raycomputed tomography system, and wherein the control system is furtherconfigured to co-register the one or more images to the magnet system.

Item 78: The magnetic particle actuating system or computer programproduct of any one of the preceding items, the wherein the controlsystem is further configured to:

receive a magnetic particle imaging signal simultaneously withapplication of the excitation field;

determine an actuation dose based at least on a calculation using themagnetic particle imaging signal; and

modify the excitation field based at least on the actuation dose.

The present disclosure contemplates that the calculations disclosed inthe embodiments herein may be performed in a number of ways, applyingthe same concepts taught herein, and that such calculations areequivalent to the embodiments disclosed.

One or more aspects or features of the subject matter described hereincan be realized in digital electronic circuitry, integrated circuitry,specially designed application specific integrated circuits (ASICs),field programmable gate arrays (FPGAs) computer hardware, firmware,software, and/or combinations thereof. These various aspects or featurescan include implementation in one or more computer programs that areexecutable and/or interpretable on a programmable system including atleast one programmable processor, which can be special or generalpurpose, coupled to receive data and instructions from, and to transmitdata and instructions to, a storage system, at least one input device,and at least one output device. The programmable system or computingsystem may include clients and servers. A client and server aregenerally remote from each other and typically interact through acommunication network. The relationship of client and server arises byvirtue of computer programs running on the respective computers andhaving a client-server relationship to each other.

These computer programs, which can also be referred to programs,software, software applications, applications, components, or code,include machine instructions for a programmable processor, and can beimplemented in a high-level procedural language, an object-orientedprogramming language, a functional programming language, a logicalprogramming language, and/or in assembly/machine language. As usedherein, the term “machine-readable medium” (or “computer readablemedium”) refers to any computer program product, apparatus and/ordevice, such as for example magnetic discs, optical disks, memory, andProgrammable Logic Devices (PLDs), used to provide machine instructionsand/or data to a programmable processor, including a machine-readablemedium that receives machine instructions as a machine-readable signal.The term “machine-readable signal” (or “computer readable signal”)refers to any signal used to provide machine instructions and/or data toa programmable processor. The machine-readable medium can store suchmachine instructions non-transitorily, such as for example as would anon-transient solid-state memory or a magnetic hard drive or anyequivalent storage medium. The machine-readable medium can alternativelyor additionally store such machine instructions in a transient manner,such as for example as would a processor cache or other random accessmemory associated with one or more physical processor cores.

To provide for interaction with a user, one or more aspects or featuresof the subject matter described herein can be implemented on a computerhaving a display device, such as for example a cathode ray tube (CRT) ora liquid crystal display (LCD) or a light emitting diode (LED) monitorfor displaying information to the user and a keyboard and a pointingdevice, such as for example a mouse or a trackball, by which the usermay provide input to the computer. Other kinds of devices can be used toprovide for interaction with a user as well. For example, feedbackprovided to the user can be any form of sensory feedback, such as forexample visual feedback, auditory feedback, or tactile feedback; andinput from the user may be received in any form, including, but notlimited to, acoustic, speech, or tactile input. Other possible inputdevices include, but are not limited to, touch screens or othertouch-sensitive devices such as single or multi-point resistive orcapacitive trackpads, voice recognition hardware and software, opticalscanners, optical pointers, digital image capture devices and associatedinterpretation software, and the like.

In the descriptions above and in the claims, phrases such as “at leastone of” or “one or more of” may occur followed by a conjunctive list ofelements or features. The term “and/or” may also occur in a list of twoor more elements or features. Unless otherwise implicitly or explicitlycontradicted by the context in which it used, such a phrase is intendedto mean any of the listed elements or features individually or any ofthe recited elements or features in combination with any of the otherrecited elements or features. For example, the phrases “at least one ofA and B;” “one or more of A and B;” and “A and/or B” are each intendedto mean “A alone, B alone, or A and B together.” A similarinterpretation is also intended for lists including three or more items.For example, the phrases “at least one of A, B, and C;” “one or more ofA, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, Balone, C alone, A and B together, A and C together, B and C together, orA and B and C together.” Use of the term “based on,” above and in theclaims is intended to mean, “based at least in part on,” such that anunrecited feature or element is also permissible.

The subject matter described herein can be embodied in systems,apparatus, methods, computer programs and/or articles depending on thedesired configuration. Any methods or the logic flows depicted in theaccompanying figures and/or described herein do not necessarily requirethe particular order shown, or sequential order, to achieve desirableresults. The implementations set forth in the foregoing description donot represent all implementations consistent with the subject matterdescribed herein. Instead, they are merely some examples consistent withaspects related to the described subject matter. Although a fewvariations have been described in detail above, other modifications oradditions are possible. In particular, further features and/orvariations can be provided in addition to those set forth herein. Theimplementations described above can be directed to various combinationsand subcombinations of the disclosed features and/or combinations andsubcombinations of further features noted above. Furthermore, abovedescribed advantages are not intended to limit the application of anyissued claims to processes and structures accomplishing any or all ofthe advantages.

Additionally, section headings shall not limit or characterize theinvention(s) set out in any claims that may issue from this disclosure.Further, the description of a technology in the “Background” is not tobe construed as an admission that technology is prior art to anyinvention(s) in this disclosure. Neither is the “Summary” to beconsidered as a characterization of the invention(s) set forth in issuedclaims. Furthermore, any reference to this disclosure in general or useof the word “invention” in the singular is not intended to imply anylimitation on the scope of the claims set forth below. Multipleinventions may be set forth according to the limitations of the multipleclaims issuing from this disclosure, and such claims accordingly definethe invention(s), and their equivalents, that are protected thereby.

What is claimed is:
 1. A computer program product comprising anon-transitory, machine-readable medium storing instructions which, whenexecuted by at least one programmable processor, cause operationscomprising: generating a magnetic field with a magnet system, themagnetic field including a field-free region at least partially matchinga target region; and applying an excitation field with an excitationsystem to cause actuation of magnetic nanoparticles in an actuationregion.
 2. The computer program product of claim 1, wherein at leastpartially matching the field-free region to the target region comprisesenclosing the target region within the field-free region.
 3. Thecomputer program product of claim 1, wherein at least partially matchingthe field-free region to the target region comprises conforming thefield-free region to the target region.
 4. The computer program productof claim 1, wherein at least partially matching the field-free region tothe target region comprises avoiding overlap with a region to avoid. 5.The computer program product of claim 1, the operations furthercomprising determining additional target region(s) during a process ofcovering an entire therapeutic region to be actuated during a treatment,while avoiding actuation of a region to avoid.
 6. The computer programproduct of claim 1, wherein the magnet system includes a first set ofmagnets on either side of the field-free region and the at leastpartially matching the field-free region to the target region includesindependently controlling at least one of the first set of magnets totranslate along a first axis.
 7. The computer program product of claim1, wherein the magnet system includes one or more electromagnets and theat least partially matching the field-free region to the target regionis based at least on controlling current(s) in the one or moreelectromagnets.
 8. The computer program product of claim 1, wherein theat least partially matching the field-free region to the target regionincludes controlling reorientation of a patient couch.
 9. The computerprogram product of claim 1, the operations further comprising applyingthe excitation field through an excitation system.
 10. The computerprogram product of claim 9, the operations further including generatingthe excitation field in a manner that changes the actuation region. 11.The computer program product of claim 9, wherein the excitation systemincludes a swappable cassette in which portions of the excitation systemare included and which can be swapped out of the magnet system fordifferent performance or different therapies.
 12. The computer programproduct of claim 1, the operations further comprising obtaining an imageof a patient, wherein the field-free region is located and/or shaped toapproximately coincide with the target region identified based at leaston the image.
 13. The computer program product of claim 12, wherein theimage is obtained from a magnetic particle imaging system.
 14. Thecomputer program product of claim 12, wherein the image is obtained froma magnetic resonance imaging system, an X-ray computed tomographysystem, an ultrasound system, or an optical fluorescence system.
 15. Thecomputer program product of claim 1, the operations further comprising:receiving a treatment plan for the target region, the treatment planspecifying the actuation to be delivered to the magnetic nanoparticles;generating or receiving one or more images of the patient; automaticallymodifying the actuation based at least on a change in the patient, achange in the magnetic nanoparticles, or a change in a predicted dose asdetermined from the one or more images; and applying the excitationfield to perform the modified actuation.
 16. The computer programproduct of claim 15, wherein modifying the actuation includes modifyinga magnitude of the excitation field or modifying a period of time ofapplying the excitation field based at least on the change in thepatient, the magnetic nanoparticles, or the predicted dose.
 17. Thecomputer program product of claim 15, the operations further comprising:receiving a magnetic particle imaging signal simultaneously withapplication of the excitation field; determining an actuation dose basedat least on a calculation using the magnetic particle imaging signal;and modifying the excitation field based at least on the actuation dose.18. A magnetic particle actuating system comprising: a magnet systemconfigured to generate a magnetic field that includes a field-freeregion; an excitation system configured to generate an excitation fieldto cause actuation of magnetic nanoparticles in an actuation region; anda control system configured to control the magnet system to create afield-free region at least partially matching a target region.
 19. Themagnetic particle actuating system of claim 18, wherein the controlsystem is further configured to control the magnet system to cause thefield-free region to enclose the target region.
 20. The magneticparticle actuating system of claim 18, wherein the control system isfurther configured to control the magnet system to cause the field-freeregion to conform to the target region.
 21. The magnetic particleactuating system of claim 18, wherein the control system is furtherconfigured to control the magnet system to cause the field-free regionto avoid overlap with a region to avoid.
 22. The magnetic particleactuating system of claim 18, wherein the control system is furtherconfigured to determine additional target region(s) for a process ofcovering an entire therapeutic region to be actuated during a treatment,while avoiding actuation of a region to avoid.
 23. The magnetic particleactuating system of claim 18, wherein the control system is furtherconfigured to control the magnet system to translate the field-freeregion to the target region as part of the at least partial matching ofthe field-free region to the target region.
 24. The magnetic particleactuating system of claim 18, wherein the control system is furtherconfigured to control the magnet system to scale the field-free regionto the target region as part of the at least partial matching of thefield-free region to the target region.
 25. The magnetic particleactuating system of claim 18, wherein the control system is furtherconfigured to control the magnet system to change a shape of thefield-free region to the target region as part of the at least partialmatching of the field-free region to the target region.
 26. The magneticparticle actuating system of claim 18, wherein the control system isfurther configured to control the magnet system to rotate the field-freeregion to the target region as part of the at least partial matching ofthe field-free region to the target region.
 27. The magnetic particleactuating system of claim 18, the magnet system further comprising: oneor more magnetic materials; and wherein the control system is furtherconfigured to cause mechanical movement of the one or more magneticmaterials to translate, scale, rotate, or change the shape of thefield-free region.
 28. The magnetic particle actuating system of claim18, the magnet system further comprising: a first set of magnets oneither side of the field-free region; and a first magnet stage systemconfigured to independently translate at least one of the first set ofmagnets along a first axis; and wherein the control system is furtherconfigured to control at least one of the first set of magnets totranslate along the first axis as part of the at least partial matchingof the field-free region to the target region.
 29. The magnetic particleactuating system of claim 28, wherein the first magnet stage system isfurther configured to independently translate the at least one of thefirst set of magnets along a second axis; and wherein the control systemis further configured to cause mechanical translation of the first setof magnets along a second axis as part of the at least partial matchingof the field-free region to the target region.
 30. The magnetic particleactuating system of claim 28, the magnet system further comprising: asecond set of magnets on either side of the field-free region; and asecond magnet stage system configured to independently translate atleast one of the second set of magnets along a second axis; and whereinthe control system is further configured to control at least one of thesecond set of magnets to translate along the second axis as part of theat least partial matching of the field-free region to the target region.31. The magnetic particle actuating system of claim 18, the magnetsystem further comprising one or more electromagnets; and wherein thecontrol system is further configured to control currents in the one ormore electromagnets as part of the at least partial matching of thefield-free region to the target region.
 32. The magnetic particleactuating system of claim 18, further comprising: a patient couch; andwherein the control system is further configured to controlreorientation of the patient couch as part of the at least partialmatching of the field-free region to the target region.
 33. The magneticparticle actuating system of claim 18, wherein the control system isfurther configured to cause the excitation system to generate theexcitation field in a manner that changes the actuation region.
 34. Themagnetic particle actuating system of claim 33, wherein the excitationsystem includes a single RF coil; and wherein the control system isfurther configured to cause the excitation system to generate theexcitation field with the single RF coil.
 35. The magnetic particleactuating system of claim 33, wherein the excitation system includesmultiple independently controllable RF coils; and wherein the controlsystem is further configured to cause the excitation system to generatethe excitation field along multiple axes utilizing the multipleindependently controllable RF coils.
 36. The magnetic particle actuatingsystem of claim 33, wherein the excitation system includes a swappablecassette containing at least a portion of the excitation system.
 37. Themagnetic particle actuating system of claim 18, further comprising an RFshield disposed between a portion of the excitation system and a portionof the magnet system to reduce interference of the excitation systemduring the generation of the excitation field.